Practical management of ibrutinib in the real life: Focus on atrial fibrillation and bleeding

Abstract

The Bruton tyrosine kinase inhibitor ibrutinib (IB) has attained an important role in the treatment of patients with chronic lymphocytic leukaemia, mantle cell lymphoma, and Waldenström macroglobulinemia, significantly improving clinical outcomes. However, IB therapy has been associated with an increased risk of atrial fibrillation (AF) and bleeding. We report on the expert opinion that a group of Italian haematologists, cardiologists, and pharmacologists jointly released to improve the practical management of patients at risk for AF and bleeding during treatment with IB. A proper pretreatment assessment to identify patients who are at a higher risk, careful choice of concomitant drugs, regular monitoring, and multispecialist approach were characterized as the main principles of clinical management of these patients. For patients developing AF, anticoagulant and antiarrhythmic therapy must be guided by considerations about efficacy, safety, and risk of pharmacokinetic interactions with IB. For patients experiencing bleeding or requiring procedures that increase the risk of bleeding, considerations about platelet turnover, IB-related platelet dysfunctions, and bleeding worsening by concomitant anticoagulants or antiplatelet agents provide clues to manage bleeding. Overall, AF and bleeding are manageable clinical events in patients receiving IB, not requiring drug interruption in most cases. Preexisting AF should not represent an absolute contraindication to IB therapy. For each patient candidate for IB, strategies of risk assessment and mitigation may allow to exploit the life-saving effects of in chronic lymphocytic leukaemia and mantle cell lymphoma.

Comorbidities and sex differences in causes of death among mantle cell lymphoma patients – A nationwide population‐based cohort study

“…BTK inhibitor use is a relative contraindication for warfarin treatment (for example for patients with paroxysmal or permanent atrial fibrillation), due to the increased bleeding risk and the long‐term increased risk of hypertension. In a recent review (Boriani et al , ), a proper pretreatment assessment, careful choice of concomitant drugs, regular monitoring, and a multidisciplinary approach were key principles in the clinical management of patients before initiation of the BTK inhibitor ibrutinib. More recently, next‐generation BTK inhibitors have emerged, such as acalabrutinib, presenting promising results and tolerability, but also a different panorama of side effects, stressing the importance of knowing the occurrence of comorbidities prior to initiation of treatment (Wang et al , ).…”

Five Ibrutinib-Associated Side Effects That All Clinicians Should Be Aware of

“…The most frequently described are atrial arrhythmias in 5–8% of treated patients, and most are atrial fibrillation [4]. However, ventricular arrhythmias and sudden cardiac death have also been described in patients receiving ibrutinib [5].…”

“…While minor bleeding events or bruising have been more commonly described, clinicians should be aware of the risk of major bleeding, including intracranial hemorrhage which may occur in up to 2% of ibrutinib-treated patients [4]. These complications may be compounded by the concurrent use of anticoagulants such as vitamin K antagonists or other direct-acting oral anticoagulants, which may potentially interact with ibrutinib.…”

“…Bleeding, another relatively frequent complication in patients treated with ibrutinib, occurs in about 3–5% of patients receiving the drug [4] and appears to be mediated by platelet dysfunction induced by BTK inhibition. While minor bleeding events or bruising have been more commonly described, clinicians should be aware of the risk of major bleeding, including intracranial hemorrhage which may occur in up to 2% of ibrutinib-treated patients [4].…”

“…The above data should be a “warning light” for clinicians to consider stopping ibrutinib therapy in patients who may have a high risk of falling and head trauma, as well as in those treated with anticoagulants. However, none of the above are considered absolute contraindications for ibrutinib treatment [4]. …”